This project is designed to understand the role of hormones (particularly prolactin and T3) in normal mammary gland development and differentiation. We also wish to determine what impact alterations in the normal thyroid hormone-prolactin balance have on mammary tumorigenesis. In addition, we wish to define any "critical periods" where such an imbalance imprints the mammary gland and results in alteration in subsequent tumor formation. Studies include: 1) evaluation of the effect of mild hypothyroidism during the pre-pubertal period as well as throughout life on formation and/or regression of hyperplastic alveolar nodules (HAN) and ultimately on mammary tumor formation; 2) examination of the ability of hypothyroidism to prevent HAN and tumor formation in animals whose tumor potential is increased by perinatal exposure to high doses of estrogens or anti-estrogens; 3) to determine what effect perinatal estrogen treatment has on pituitary function and lactogenic receptors; 4) to characterize the nature of interaction of prolactin and human growth hormone with native as well as cryptic forms of lactogenic receptors, and 5) to partially purify the lactogenic receptor in order to produce monoclonal antibodies against it.